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Biomedical subjects

G Valentini

Publications and source records attributed to G Valentini.

At least 37 records · Page 2Linked to original sources
PubMed2003

Assessment of disease activity.

The objective of this study was to select a simple, feasible and validated core set of variables for the assessment of disease activity in systemic sclerosis. The subcommittee members extensively reviewed the studies in which the disease activity had been assessed, and analysed the construct validity and the feasibility of the criteria used in each study. The subcommittee members agreed on the possible use of either the European Scleroderma Study Group (ESSG) criteria for disease activity in SSc or the evaluation of selected cytokines and cell activation markers, found to be associated with distinct organ system involvement in recent studies. Despite the potential usefulness of cytokines and activation markers, most participants in the plenary session retained that their evaluation is not feasible in a number of centres, and their construct validity has not yet been assessed. The ESSG criteria for disease activity can be used for the time being to assess disease activity in clinical investigation studies as well as in clinical practice.

Biomarkers↗
PubMed2003

[Physiopathologic approach in esophageal motor disorders: from the diagnosis to therapeutic implications].

Motor disorders are an important chapter in esophageal pathology; from a clinical point of view, these disorders are characterised by dysphagia, non-cardiac chest pain, pyrosis and regurgitation. It is important to underline that chest pain and dysphagia are not specific to motility disorders; in fact, they are also present in other pathologies like peptic or infective esophagitis. In order to attribute these symptoms to a functional cause, it is first of all is necessary to exclude an organic pathology; this can be done with the help of radiological and endoscopical examination when the symptoms are dysphagia, pyrosis and regurgitation, or with electrocardiography or angiography, when the symptom is chest pain. The functional pathology is marines studied by manometric and pH-metric techniques. The manometric technique represents an important instrument for diagnosing esophageal motor disease. The aim of this study, after a review of the literature, is to describe the principal esophageal motor disorders and the physiopathological approach, that have important implications in diagnosis and therapy.

English Abstract↗
PubMed2002

[Whipple's disease: progress in the diagnosis and review of the literature].

Whipple's disease is a rare, chronic, multisystemic disease characterized by the presence of fever, diarrhea, weight loss and malabsorption, preceded by arthritis. Although Whipple's disease almost always includes involvement of the small intestine and the presence of malabsorption, it commonly affects other organs, especially the heart, brain, eyes and joints. Whipple's disease greately mimics other diseases and is caused by a cultivation-resistant bacterium. The disease is fatal unless patients are treated with antibiotics. The diagnosis of Whipple's disease can be made by histologic analysis of small-intestinal biopsy specimens. Identification of Whipple bacterium, Tropheryma whippelii, has led to the development of the polymerase chain reaction This technique can be used to detect the bacterium in many organs and fluids, including synovial tissue and fluid. Affected patients tend to have dilated intestinal villi that are infiltrated with foamy macrophages.

Anti-Bacterial Agents↗
PubMed2002

Enteral diet in Crohn's disease. Nutritional and therapeutic implications in patient's management.

Inflammatory bowel diseases (IBD) are often characterized by impairment of nutritional status. Crohn's disease (CD) patients, especially in the active phase of disease, show a reduced body weight, due to the reduction of lipid stores, in spite of lean mass depletion. Fat mass reduction has been correlated to an increased utilization of lipids as fuel substrate. The alterations of nutritional status are able, in turn, to influence, as independent factors, the disease course and patient prognosis. A disease's treatment based only on pharmacologic therapy, especially on corticosteroid use in the active phases, often does not take into account the relevant need for preserving a normal nutritional status. In this connection, enteral nutrition has been shown to be able to improve nutritional status and induce and maintain remission. We present some of the possible mechanisms of efficacy of enteral feeding and some rules to attempt to treat patients with IBD, especially those with Crohn's disease.

Journal Article↗
PubMed2002

Main physiopathologic mechanisms involved in hepatic drug reactions.

The liver has a pivotal role in drug metabolism and hepatic drug reactions are frequent events, accounting for 5% of cases of jaundice or acute hepatitis in the community. The importance of hepatic drug reactions lies not only in their frequency, but also in the great number of molecules that can cause this type of lesions and in their variable gravity. This review will show the main factors implicated in drug metabolism which can explain the different susceptibility in developing hepatic drug reaction, the possibility that it may manifest as a wide spectrum of clinical syndromes or that a single agent may cause more than one lesion (a relevant problem not only for the clinician, but also for the pathologist).

Journal Article↗
PubMed2001

Human erythrocyte pyruvate kinase: characterization of the recombinant enzyme and a mutant form (R510Q) causing nonspherocytic hemolytic anemia.

Human erythrocyte pyruvate kinase plays an important role in erythrocyte metabolism. Mutation on the gene results in pyruvate kinase deficiency and is an important cause of hereditary nonspherocytic hemolytic anemia. Because of difficulties in isolating the mutant enzymes from patients, these mutations have not been fully studied. In this study, a complementary DNA (cDNA) encoding the human erythrocyte pyruvate kinase was generated. The cDNA was cloned into several expression vectors, and the protein was expressed and purified. The tetrameric protein exhibited properties characteristic of authentic human erythrocyte pyruvate kinase, including response to substrate, phosphoenolpyruvate, activation by fructose 1,6-bisphosphate, and inhibition by adenosine triphosphate (ATP). The N-terminal segment of the protein was highly susceptible to proteolysis, but only 2 of the 4 subunits were cleaved and lacked 47 N-terminal amino acid residues. A mutant protein, R510Q, which is the most frequently occurring mutation among Northern European population, was also generated and purified. The mutant protein retained its binding capacity to and could be activated by fructose 1,6-bisphosphate and showed similar kinetics toward phosphoenolpyruvate and adenosine diphosphate as for the wild-type enzyme. Conversely, the mutant protein has a dramatically decreased stability toward heat and is more susceptible to ATP inhibition. The enzyme instability decreases the enzyme level in the cell, accounting for the clinically observed "pyruvate kinase deficiency" of patients who are homozygous for this mutation. This study provides the first detailed functional characterization of human erythrocyte pyruvate kinase. These findings will allow the establishment of a fine correlation between molecular abnormalities and the clinical expression of the disease.

Adenosine Triphosphate↗
PubMed2001

Inhibition of heat-induced denaturation of albumin by nonsteroidal antiinflammatory drugs (NSAIDs): pharmacological implications.

The activity of nonsteroidal antiinflammatory drugs (NSAIDs) in rheumatoid arthritis is not only due to the inhibition of the production of prostaglandins, which can even have beneficial immunosuppressive effects in chronic inflammatory processes. Since we speculated that these drugs could also act by protecting endogenous proteins against denaturation, we evaluated their effect on heat-induced denaturation human serum albumin (HSA) in comparison with several fatty acids which are known to be potent stabilizers of this protein. By the Mizushimas assay and a recently developed HPLC assay, we observed that NSAIDs were slightly less active [EC50 to approximately 10(-5)-10(-4) M] than FA and that the HPLC method was less sensitive but more selective than the turbidimetric assay, i.e. it was capable of distinguishing true antiaggregant agents like FA and NSAIDs from substances capable of inhibiting the precipitation of denatured protein aggregates. In conclusion, this survey could be useful for the development of more effective agents in protein condensation diseases like rheumatic disorders, cataract and Alzheimers disease.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2001

Effects of photodynamic therapy on the absorption properties of disulphonated aluminum phthalocyanine in tumor-bearing mice.

Time-resolved reflectance spectroscopy was performed on tumor-bearing mice, administered with disulphonated aluminum phthalocyanine (AlS(2)Pc, 5 mg/kg body weight), before, during and after photodynamic therapy. This allowed us to evaluate the absorption spectrum of AlS(2)Pc in vivo from 610 to 700 nm, and to investigate how the therapeutic irradiation affects it. Two tumor locations (intraderma on the back and intramuscular in the leg), and two uptake times (3 and 12 h) were considered. As already observed previously, the absorption spectrum of AlS(2)Pc in vivo is centered at 680-685 nm. The irradiation causes a blue-shift of the measured line shape, more or less marked depending on the experimental conditions. A reduction in absorption is also often observed upon illumination with therapeutic light doses.

Absorption↗
PubMed2001

Proximal stomach function in systemic sclerosis: relationship with autonomic nerve function.

Gastrointestinal involvement is frequent in patients with systemic sclerosis (SSc); however, studies on the proximal stomach and its regulation are lacking. It has been hypothesized that the primary event in the pathogenesis of gastrointestinal involvement in SSc is an early neural lesion. This study investigates proximal stomach function and its relation to autonomic nerve function in SSc. Twenty SSc patients classified in to clinical subsets, underwent measurement of proximal stomach function with and without glucagon by electronic barostat and an assessment of autonomic nerve function. SSc patients were not significantly different from 11 controls for gastric compliance (59.5+/-5.0 vs 47.7+/-4.2 ml/mm Hg, P = 0.1). The pressure-volume curves in each participant with and without glucagon were significantly different (P < 0.001). A significant positive association was found between gastric compliance and autonomic nerve function (P < 0.05). The change in gastric compliance during glucagon administration was significant-associated with autonomic function (P < 0.05). The perception cumulative scores did not differ between SSc patients and control subjects (P = 0.2). In conclusion, proximal stomach function is associated with autonomic nerve function in SSc patients. This confirms the frequent association of motility disorders with autonomic dysfunction in SSc.

Adult↗
PubMed2001

Peripheral blood T lymphocytes from systemic sclerosis patients show both Th1 and Th2 activation.

Our objective was to investigate the phenotype of helper T cells in the peripheral blood of patients with systemic sclerosis (SSc). PBMC from 15 patients with SSc and 15 sex- and age-matched controls were investigated for lymphocyte subpopulations (CD3, CD4, CD8, CD19, CD16/CD56, CD3-DR); IL-2, IL-4, and IFN-gamma mRNAs; and the relative cytokines in their cytoplasm. The last assay was carried out both in unstimulated and in PMA-activated PBMC. SSc patients presented a higher percentage of activated T cells, CD3+ DR+ (19.7 +/- 9.9 vs 5.1 +/- 2.5%; P < 0.0001); 12 of them presented IFN-gamma mRNA-positive cells; and none IL-2 or IL-4 mRNAs. Under basal conditions, PBMC from six SSc patients contained IL-2, IL-4, and IFN-gamma (i.e., they showed both Th1 and Th2 activation), and 1 IFN-gamma only. PMA-stimulated PBMC of patients differed from those of controls only in the increased percentage of IFN-gamma positive cells (52 +/- 12 vs 37 +/- 11%; P < 0.01). Our study demonstrates that Thl activation occurs in the peripheral blood of SSc patients. This evidence must be faced with from both a pathogenetic and a therapeutical point of view.

Adult↗
PubMed2001

European multicentre study to define disease activity criteria for systemic sclerosis. I. Clinical and epidemiological features of 290 patients from 19 centres.

OBJECTIVE: To investigate the existence of differences among European referral centres for systemic sclerosis (SSc) in the pattern of attendance and referral and in the clinical and therapeutical approaches. METHODS: In 1995 the European Scleroderma Study Group initiated a multicentre prospective one year study whose aim was to define the disease activity criteria in SSc. During the study period each participating European centre was asked to enroll consecutive patients satisfying American College of Rheumatology criteria for SSc and to fill out for each of them a standardised clinical chart. Patients from various centres were compared and differences in epidemiological, clinical, and therapeutical aspects were analysed. RESULTS: Nineteen different medical research centres consecutively recruited 290 patients. The patients could be divided into two subgroups: 173 with the limited (lSSc) and 117 with the diffuse (dSSc) form of the disease. The clinical and serological findings for the series of 290 patients seemed to be similar to data previously reported. However, when the data were analysed to elicit any differences between the participating centres, a high degree of variability emerged, in both epidemiological and clinical features and in the diagnostic and therapeutic approaches to the disease. CONCLUSIONS: The clinical approach to SSc, not only in different countries but also in different centres within the same country, is not yet standardised. To overcome this problem, it will be necessary for the scientific community to draw up a standardised procedure for the management of patients with SSc. This would provide a common research tool for different centres engaged in research on this complex disease.

Adolescent↗
PubMed2001

European multicentre study to define disease activity criteria for systemic sclerosis. II. Identification of disease activity variables and development of preliminary activity indexes.

OBJECTIVE: To develop criteria for disease activity in systemic sclerosis (SSc) that are valid, reliable, and easy to use. METHODS: Investigators from 19 European centres completed a standardised clinical chart for a consecutive number of patients with SSc. Three protocol management members blindly evaluated each chart and assigned a disease activity score on a semiquantitative scale of 0-10. Two of them, in addition, gave a blinded, qualitative evaluation of disease activity ("inactive to moderately active" or "active to very active" disease). Both these evaluations were found to be reliable. A final disease activity score and qualitative evaluation of disease activity were arrived at by consensus for each patient; the former represented the gold standard for subsequent analyses. The correlations between individual items in the chart and this gold standard were then analysed. RESULTS: A total of 290 patients with SSc (117 with diffuse SSc (dSSc) and 173 with limited SSc (lSSc)) were enrolled in the study. The items (including Delta-factors-that is, worsening according to the patient report) that were found to correlate with the gold standard on multiple regression were used to construct three separate 10-point indices of disease activity: (a) Delta-cardiopulmonary (4.0), Delta-skin (3.0), Delta-vascular (2.0), and Delta-articular/muscular (1.0) for patients with dSSc; (b) Delta-skin (2.5), erythrocyte sedimentation rate (ESR) >30 mm/1st h (2.5), Delta-cardiopulmonary (1.5), Delta-vascular (1.0), arthritis (1.0), hypocomplementaemia (1.0), and scleredema (0.5) for lSSc; (c) Delta-cardiopulmonary (2.0), Delta-skin (2.0), ESR >30 mm/1st h (1.5), total skin score >20 (1.0), hypocomplementaemia (1.0), scleredema (0.5), digital necrosis (0.5), Delta-vascular (0.5), arthritis (0.5), TLCO <80% (0.5) for all patients with SSc. The three indexes were validated by the jackknife technique. Finally, receiver operating characteristic curves were constructed in order to define the value of the index with the best discriminant capacity for "active to very active" patients. CONCLUSIONS: Three feasible, reliable, and valid preliminary indices to define disease activity in SSc were constructed.

Adolescent↗
PubMed2001

Intravenous N-acetylcysteine for treatment of Raynaud's phenomenon secondary to systemic sclerosis: a pilot study.

OBJECTIVE: To assess the efficacy and tolerability of N-acetylcysteine (NAC) in patients with Raynaud's phenomenon (RP) secondary to systemic sclerosis (scleroderma; SSc). METHODS: Twenty-two patients with RP secondary to SSc were enrolled in a multicenter, open clinical trial lasting 11 weeks and conducted in winter. Primary outcome measures were frequency and severity of RP attacks, and number of digital ulcers. Secondary outcome measure was improvement in digital cold challenge test assessed by photoelectric plethysmography. Patients received a continuous 5 day intravenous infusion of NAC starting with a 2 h loading dose of 150 mg/kg subsequently adjusted to 15 mg/kg/h. RESULTS: All 22 patients completed the 5 day infusion and 20 of them the posttreatment followup. Both frequency and severity of RP attacks decreased significantly compared to pretreatment values. Active ulcers were significantly less numerous at all followup visits (25.18% of baseline count on Day 33 from the beginning of infusion). In the cold challenge test mean recovery time fell by 69.56%, 67.70%, 71.42%, and 71.05% on Days 12, 19. 33, and 61 from the beginning of treatment. Side effects were minor, easily controlled, and reversible. CONCLUSION: N-acetylcysteine appears to be safe for the treatment of RP secondary to SSc. These preliminary data warrant further controlled studies.

Acetylcysteine↗
PubMed2000

The allosteric regulation of pyruvate kinase.

Pyruvate kinase (PK) is critical for the regulation of the glycolytic pathway. The regulatory properties of Escherichia coli were investigated by mutating six charged residues involved in interdomain salt bridges (Arg(271), Arg(292), Asp(297), and Lys(413)) and in the binding of the allosteric activator (Lys(382) and Arg(431)). Arg(271) and Lys(413) are located at the interface between A and C domains within one subunit. The R271L and K413Q mutant enzymes exhibit altered kinetic properties. In K413Q, there is partial enzyme activation, whereas R271L is characterized by a bias toward the T-state in the allosteric equilibrium. In the T-state, Arg(292) and Asp(297) form an intersubunit salt bridge. The mutants R292D and D297R are totally inactive. The crystal structure of R292D reveals that the mutant enzyme retains the T-state quaternary structure. However, the mutation induces a reorganization of the interface with the creation of a network of interactions similar to that observed in the crystal structures of R-state yeast and M1 PK proteins. Furthermore, in the R292D structure, two loops that are part of the active site are disordered. The K382Q and R431E mutations were designed to probe the binding site for fructose 1, 6-bisphosphate, the allosteric activator. R431E exhibits only slight changes in the regulatory properties. Conversely, K382Q displays a highly altered responsiveness to the activator, suggesting that Lys(382) is involved in both activator binding and allosteric transition mechanism. Taken together, these results support the notion that domain interfaces are critical for the allosteric transition. They couple changes in the tertiary and quaternary structures to alterations in the geometry of the fructose 1, 6-bisphosphate and substrate binding sites. These site-directed mutagenesis data are discussed in the light of the molecular basis for the hereditary nonspherocytic hemolytic anemia, which is caused by mutations in human erythrocyte PK gene.

Arginine↗
PubMed2000

Preliminary evaluation of two fluorescence imaging methods for the detection and the delineation of basal cell carcinomas of the skin.

BACKGROUND AND OBJECTIVE: Fluorescence techniques can provide powerful noninvasive means for medical diagnosis, based on the detection of either endogenous or exogenous fluorophores. The fluorescence of delta-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) has already shown promise for the diagnosis of tumors. The aim of the study was to investigate the localization of skin tumors after the topical application of ALA, by detecting the PpIX fluorescence either in the spectral or in the time domain. STUDY DESIGN/MATERIALS N AND METHODS: Two fluorescence imaging systems were used to identify basal cell carcinomas of the skin in humans, after topical application of 20% ALA ointment. Both systems rely on the comparison between the exogenous and the endogenous fluorescence, performed either in the spectral domain or in the time domain. The first system works by using three images acquired through different spectral filters, whereas the second one measures the spatial map of the average fluorescence lifetime of the sample. RESULTS: A clear demarcation of skin malignancies was successfully performed in vivo noninvasively with both fluorescence imaging systems. CONCLUSION: The two complementary approaches considered in the present study show promise for skin tumor detection and delineation based on specific fluorescence features.

Adult↗